Viral Hepatitis Drugs

Question 1

acyclic phosphonates

Answer 1

adefovir dipivoxil

tenofovir disoproxil

Question 2

adefovir MOA

Answer 2

adenosine-5-monophosphate - diphosphate form incorporated into viral DNA producing chain termination

Question 3

adefovir tox

Answer 3

Hepatic tox

Question 4

adefovir PK

Answer 4

8 hr half life, rapid hydrolysis to adefovir; excreted in urine (GFR + RTS)

Question 5

tenofovir disoproxil MOA

Answer 5

pro-drug for tenofovir, a nucleotide analog of adenosine-5-monophosphate - diphosphate form inhibits HBV polymerase & produces chain termination

Question 6

tenofovir tox

Answer 6

acute renal failure (check Cr/BUN)
bone fractures/pain
osteoporosis (give Ca and Vit D supplements)

Question 7

tenofovir pk

Answer 7

17 hour half life, intracellular hydrolysis to tenofovir; excreted unchanged in urine (GFR + RTS) and high fat meal IMPROVES bio availability

Question 8

L-nucleosides

Answer 8

lamivudine (3TC)

emtricitabine

Question 9

l-nucleoside MOA

Answer 9

L-isomers of cytosine with similar activity, potency, side effects and patterns of resistance - triphosphate form inhibits HBV polymerase

Question 10

lamivudine PK

Answer 10

7 hour half life, excreted unchanged in urine (GFR + RTS)

Question 11

emtricitabine PK

Answer 11

10 hour half life, excreted unchanged in urine (GFR + RTS)

Question 12

d-cyclopentane

Answer 12

entecavir

Question 13

entecavir MOA

Answer 13

Guanosine nucleoside analog - triphosphate form inhibits HBV polymerase

Question 14

entecavir tox

Answer 14

hepatic tox

Question 15

etecavir PK

Answer 15

130 hour half life, NO CYP INTERACTION, excreted unchanged in urine and food DELAYS absorption

Question 16

IFN MOA (6 effects)

Answer 16

1. antiviral & antiproliferative, with immunomodulatory effects.
2. activates tyrosine kinase and IFN
3. endoribonucleases cleave ssRNA
4. inhibitor effect on dsRNA
5. inhibition of viral penetration & release
6. enhanced lytic effect on ctyoT lymphocytes

Question 17

IFN AE

Answer 17

FLS, neuropsychiatric, myelosuppression with granulocytopenia, increased hepatic enzymes and triglycerides, destruction of thyroid (genetic based)

Question 18

IFN-PEG AE

Answer 18

same as IFN but better tolerated

Question 19

3 treatments for HCV

Answer 19

ribavirin, telaprevir, bocepravir

Question 20

ribavirin MOA

Answer 20

1. enhanced host T-cell clearance
2. inhibition of IMPDH, deplete GTP
3. direct inhibition of HCV RNA pol

Question 21

ribavirin AE

Answer 21

hemolytic anemia, fatal/non-fatal MI, difficulty breathing, MALE mediated teratogenicity

Question 22

ribavirin PK

Answer 22

always give with IFN. has increased bioavailability with high fat meal
NO CYP but renal accumulation
extensive uptake by cells (RBCs)

Question 23

telaprevir and bocepravir MOA

Answer 23

NS3/4A serine protease inhibitors, inhibits cleavage of key proteins
resistance is major issue

Question 24

AE telaprevir

Answer 24

pruritus and rash (BBW)

Question 25

AE boceprevir

Answer 25

anemia, fatigue, nausea

Question 26

telaprevir & bocepravir PK

Answer 26

oral, take with food (high fat for telaprevir)
less effective in african americans
hepatic metabolism (CYP3A4, p-gp)

Question 27

telaprevir & bocepravir CI/DDI

Answer 27

CI with CYP3A4 inducers

Question 28

HCV G1 treatment

Answer 28

pegIFN + Rib + Tel/Boc

Question 29

HCV G2/3 treatment

Answer 29

pegIFN + Rib